{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:31:03Z","timestamp":1790857863739,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,26]],"date-time":"2019-10-26T00:00:00Z","timestamp":1572048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009232","name":"Debreceni Egyetem","doi-asserted-by":"publisher","award":["1G3D BKJ0 BFTK 247"],"award-info":[{"award-number":["1G3D BKJ0 BFTK 247"]}],"id":[{"id":"10.13039\/501100009232","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tempus Foundation, Stipendium Hungaricum","award":["1Q4D BKX5 STIP 320"],"award-info":[{"award-number":["1Q4D BKX5 STIP 320"]}]},{"name":"International Education Office, University of Debrecen, Debrecen","award":["1G3D BK00 BMCK 247"],"award-info":[{"award-number":["1G3D BK00 BMCK 247"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Huntington\u2019s disease (HD) is an inherited neurodegenerative disorder, caused by an abnormal polyglutamine (polyQ) expansion in the huntingtin protein (Htt). Mitochondrial dysfunction and impairment of the ubiquitin-proteasome system (UPS) are hallmarks of HD neurons. The extraneural manifestations of HD are still unclear. We investigated the crosstalk between mitochondria and proteolytic function in skin fibroblasts from juvenile HD patients. We found reduced mitosis, increased cell size, elevated ROS and increased mitochondrial membrane potential in juvenile HD fibroblasts, while cellular viability was maintained. Mitochondrial OXPHOS analysis did not reveal significant differences compared to control. However, the level of mitochondrial fusion and fission proteins was significantly lower and branching in the mitochondria network was reduced. We hypothesized that juvenile HD fibroblasts counterbalance cellular damage and mitochondrial network deficit with altered proteasome activity to promote cell survival. Our data reveal that juvenile HD fibroblasts exhibit higher proteasome activity, which was associated with elevated gene and protein expression of parkin. Moreover, we demonstrate elevated proteasomal degradation of the mitochondrial fusion protein Mfn1 in diseased cells compared to control cells. Our data suggest that juvenile HD fibroblasts respond to mutant polyQ expansion of Htt with enhanced proteasome activity and faster turnover of specific UPS substrates to protect cells.<\/jats:p>","DOI":"10.3390\/ijms20215338","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T04:44:31Z","timestamp":1572237871000},"page":"5338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Juvenile Huntington\u2019s Disease Skin Fibroblasts Respond with Elevated Parkin Level and Increased Proteasome Activity as a Potential Mechanism to Counterbalance the Pathological Consequences of Mutant Huntingtin Protein"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5666-8585","authenticated-orcid":false,"given":"Azzam","family":"Aladdin","sequence":"first","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1606-3132","authenticated-orcid":false,"given":"R\u00f3bert","family":"Kir\u00e1ly","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pal","family":"Boto","sequence":"additional","affiliation":[{"name":"Stem Cell Differentiation Laboratory, Department of Biochemistry and Molecular Biology, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Regdon","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1810-0128","authenticated-orcid":false,"given":"Krisztina","family":"Tar","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S1474-4422(10)70245-3","article-title":"Huntington\u2019s Disease: From Molecular Pathogenesis to Clinical Treatment","volume":"10","author":"Ross","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/brain\/awg077","article-title":"Homozygosity for CAG Mutation in Huntington Disease is Associated with a More Severe Clinical Course","volume":"126","author":"Squitieri","year":"2003","journal-title":"Brain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1146\/annurev.neuro.29.051605.113042","article-title":"Trinucleotide Repeat Disorders","volume":"30","author":"Orr","year":"2007","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Koyuncu, S., Fatima, A., Gutierrez-Garcia, R., and Vilchez, D. (2017). Proteostasis of Huntingtin in Health and Disease. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071568"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.ejphar.2012.10.026","article-title":"Late Onset Vascular Dysfunction in the R6\/1 Model of Huntington\u2019s Disease","volume":"698","author":"Rahman","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10127","DOI":"10.1038\/s41598-019-46470-8","article-title":"Peripheral Expression of Mutant Huntingtin is a Critical Determinant of Weight Loss and Metabolic Disturbances in Huntington\u2019s Disease","volume":"9","author":"Lakra","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1091\/mbc.E18-09-0590","article-title":"A Patient-Derived Cellular Model for Huntington\u2019s Disease Reveals Phenotypes at Clinically Relevant CAG Lengths","volume":"29","author":"Hung","year":"2018","journal-title":"Mol. Boil. Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e275","DOI":"10.1212\/NXG.0000000000000275","article-title":"Bioenergetics in Fibroblasts of Patients with Huntington Disease are Associated with Age at Onset","volume":"4","author":"Gardiner","year":"2018","journal-title":"Neurol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s11064-006-9110-2","article-title":"Oxidative Stress in Skin Fibroblasts Cultures of Patients with Huntington\u2019s Disease","volume":"31","author":"Molina","year":"2006","journal-title":"Neurochem. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1007\/s11011-018-0308-1","article-title":"Mitochondrial Alterations Accompanied by Oxidative Stress Conditions in Skin Fibroblasts of Huntington\u2019s Disease Patients","volume":"33","author":"Mozolewski","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jns.2013.11.014","article-title":"Gene Expression Profile in Fibroblasts of Huntington\u2019s Disease Patients and Controls","volume":"337","author":"Marchina","year":"2014","journal-title":"J. Neurol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.nbd.2015.09.008","article-title":"Mitochondrial Dynamics and Quality Control in Huntington\u2019s Disease","volume":"90","author":"Pinho","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1007\/s12640-017-9766-1","article-title":"Huntington\u2019s Disease and Mitochondria","volume":"32","author":"Farshbaf","year":"2017","journal-title":"Neurotox. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1093\/hmg\/ddr024","article-title":"Abnormal Mitochondrial Dynamics, Mitochondrial Loss and Mutant Huntingtin Oligomers in Huntington\u2019s Disease: Implications for Selective Neuronal Damage","volume":"20","author":"Shirendeb","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.bbadis.2011.10.016","article-title":"Mutant Huntingtin, Abnormal Mitochondrial Dynamics, Defective Axonal Transport of Mitochondria, and Selective Synaptic Degeneration in Huntington\u2019s Disease","volume":"1822","author":"Reddy","year":"2012","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/hmg\/ddr475","article-title":"Mutant Huntingtin\u2019s Interaction with Mitochondrial Protein Drp1 Impairs Mitochondrial Biogenesis and Causes Defective Axonal Transport and Synaptic Degeneration in Huntington\u2019s Disease","volume":"21","author":"Shirendeb","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Parone, P.A., Da Cruz, S., Tondera, D., Mattenberger, Y., James, D.I., Maechler, P., Barja, F., and Martinou, J.C. (2008). Preventing Mitochondrial Fission Impairs Mitochondrial Function and Leads to Loss of Mitochondrial DNA. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003257"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.molcel.2012.12.003","article-title":"Two Deubiquitylases Act on Mitofusin and Regulate Mitochondrial Fusion along Independent Pathways","volume":"49","author":"Anton","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1242\/jcs.03381","article-title":"Mitochondrial Bioenergetics and Structural Network Organization","volume":"120","author":"Benard","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1016\/j.bbabio.2012.02.033","article-title":"Bioenergetic Role of Mitochondrial Fusion and Fission","volume":"1817","author":"Westermann","year":"2012","journal-title":"Biochim. Biophys. Acta. (BBA) Gen. Subj."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cmet.2018.01.011","article-title":"Circadian Control of DRP1 Activity Regulates Mitochondrial Dynamics and Bioenergetics","volume":"27","author":"Schmitt","year":"2018","journal-title":"Cell Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"452","DOI":"10.3389\/fgene.2018.00452","article-title":"Circadian Rhythms and Mitochondria: Connecting the Dots","volume":"9","author":"Puig","year":"2018","journal-title":"Front. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1089\/ars.2010.3779","article-title":"The Interplay Between Mitochondrial Dynamics and Mitophagy","volume":"14","author":"Twig","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/j.biocel.2011.06.002","article-title":"Ubiquitin-Dependent Mitochondrial Protein Degradation","volume":"43","author":"Heo","year":"2011","journal-title":"Int. J. Biochem. Cell Boil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"170007","DOI":"10.1098\/rsob.170007","article-title":"Control of Mitochondrial Biogenesis and Function by the Ubiquitin\u2013Proteasome System","volume":"7","author":"Bragoszewski","year":"2017","journal-title":"Open Boil."},{"key":"ref_26","first-page":"35","article-title":"Interplay Between the Ubiquitin Proteasome System and Mitochondria for Protein Homeostasis","volume":"35","author":"Altin","year":"2019","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_27","first-page":"1","article-title":"Relationship Between the Proteasomal System and Autophagy","volume":"4","author":"Lilienbaum","year":"2013","journal-title":"Int. J. Biochem. Mol. Boil."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"441","DOI":"10.14348\/molcells.2017.0115","article-title":"Crosstalk and Interplay Between the Ubiquitin-Proteasome System and Autophagy","volume":"40","author":"Ji","year":"2017","journal-title":"Mol. Cells"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.molcel.2010.12.020","article-title":"Proteasome Activators","volume":"41","author":"Stadtmueller","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"42830","DOI":"10.1074\/jbc.M111.300178","article-title":"Blm10 Protein Promotes Proteasomal Substrate Turnover by an Active Gating Mechanism","volume":"286","author":"Dange","year":"2011","journal-title":"J. Boil. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/j.str.2017.07.013","article-title":"The Mammalian Proteasome Activator PA28 Forms an Asymmetric \u03b14\u03b23 Complex","volume":"25","author":"Huber","year":"2017","journal-title":"Structure"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1091\/mbc.12.5.1393","article-title":"Accumulation of Mutant Huntingtin Fragments in Aggresome-like Inclusion Bodies as a Result of Insufficient Protein Degradation","volume":"12","author":"Waelter","year":"2001","journal-title":"Mol. Boil. Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/jnc.12647","article-title":"Sulforaphane Enhances Proteasomal and Autophagic Activities in Mice and is a Potential Therapeutic Reagent for Huntington\u2019s Disease","volume":"129","author":"Liu","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1083\/jcb.201110093","article-title":"Indirect Inhibition of 26S Proteasome Activity in a Cellular Model of Huntington\u2019s Disease","volume":"196","author":"Hipp","year":"2012","journal-title":"J. Cell Boil."},{"key":"ref_35","first-page":"837015","article-title":"The Ubiquitin-Proteasome System in Huntington\u2019s Disease: Are Proteasomes Impaired, Initiators of Disease, or Coming to the Rescue?","volume":"2012","author":"Juenemann","year":"2012","journal-title":"Biochem. Res. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"27068","DOI":"10.1074\/jbc.M113.486076","article-title":"Expanded Polyglutamine-Containing N-Terminal Huntingtin Fragments Are Entirely Degraded by Mammalian Proteasomes*","volume":"288","author":"Juenemann","year":"2013","journal-title":"J. Boil. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4587691","DOI":"10.1155\/2016\/4587691","article-title":"Cross Talk of Proteostasis and Mitostasis in Cellular Homeodynamics, Ageing, and Disease","volume":"2016","author":"Gumeni","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6798712","DOI":"10.1155\/2018\/6798712","article-title":"Proteostasis and Mitochondrial Role on Psychiatric and Neurodegenerative Disorders: Current Perspectives","volume":"2018","author":"Olivero","year":"2018","journal-title":"Neural Plast."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41593-018-0075-7","article-title":"Striatal Neurons Directly Converted from Huntington\u2019s Disease Patient Fibroblasts Recapitulate Age-Associated Disease Phenotypes","volume":"21","author":"Victor","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Liu, Y., Xue, Y., Ridley, S., Zhang, D., Rezvani, K., Fu, X.D., and Wang, H. (2014). Direct Reprogramming of Huntington\u2019s Disease Patient Fibroblasts into Neuron-Like Cells Leads to Abnormal Neurite Outgrowth, Increased Cell Death, and Aggregate Formation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109621"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13024-015-0018-7","article-title":"Making (Anti-) Sense Out of Huntingtin Levels in Huntington Disease","volume":"10","author":"Evers","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3233\/JHD-170261","article-title":"Neuropathological Comparison of Adult Onset and Juvenile Huntington\u2019s Disease with Cerebellar Atrophy: A Report of a Father and Son","volume":"6","author":"Latimer","year":"2017","journal-title":"J. Huntingt. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e1939","DOI":"10.1212\/WNL.0000000000007355","article-title":"Brain Structure in Juvenile-Onset Huntington Disease","volume":"92","author":"Tereshchenko","year":"2019","journal-title":"Neurology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3233\/JHD-180339","article-title":"Clinical Presentation and Features of Juvenile-Onset Huntington\u2019s Disease: A Systematic Review","volume":"8","author":"Cronin","year":"2019","journal-title":"J. Huntingt. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0304-3940(99)00578-9","article-title":"Oxidative Damage to Mitochondrial DNA in Huntington\u2019s Disease Parietal Cortex","volume":"272","author":"Polidori","year":"1999","journal-title":"Neurosci. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.freeradbiomed.2008.05.014","article-title":"Proteomic and Oxidative Stress Analysis in Human Brain Samples of Huntington Disease","volume":"45","author":"Sorolla","year":"2008","journal-title":"Free. Radic. Boil. Med."},{"key":"ref_47","first-page":"376","article-title":"Oxidative Stress in Neurodegenerative Diseases","volume":"7","author":"Chen","year":"2012","journal-title":"Neural Regen. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3233\/JHD-160205","article-title":"Oxidative Stress and Huntington\u2019s Disease: The Good, The Bad, and The Ugly","volume":"5","author":"Kumar","year":"2016","journal-title":"J. Huntingt. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/1873-3468.12964","article-title":"Role of Mitochondrial ROS in the Brain: From Physiology to Neurodegeneration","volume":"592","author":"Angelova","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"329","DOI":"10.3389\/fnmol.2018.00329","article-title":"A Mitochondria-Associated Oxidative Stress Perspective on Huntington\u2019s Disease","volume":"11","author":"Zheng","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00018-017-2603-0","article-title":"The Ever-Growing Complexity of the Mitochondrial Fission Machinery","volume":"75","author":"Pagliuso","year":"2018","journal-title":"Cell Mol. Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1083\/jcb.201511036","article-title":"Metabolic Regulation of Mitochondrial Dynamics","volume":"212","author":"Mishra","year":"2016","journal-title":"J. Cell Boil."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.cmet.2017.05.016","article-title":"Mitochondrial Dynamics in Regulating the Unique Phenotypes of Cancer and Stem Cells","volume":"26","author":"Chen","year":"2017","journal-title":"Cell Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/ana.20207","article-title":"Generalized Brain and Skin Proteasome Inhibition in Huntington\u2019s Disease","volume":"56","author":"Seo","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0076-6879(05)98029-4","article-title":"Characterization of the Proteasome Using Native Gel Electrophoresis","volume":"398","author":"Elsasser","year":"2005","journal-title":"Methods Enzym."},{"key":"ref_56","first-page":"237","article-title":"Native Gel Approaches in Studying Proteasome Assembly and Chaperones","volume":"1844","author":"Roelofs","year":"2018","journal-title":"Adv. Struct. Saf. Stud."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-1-59745-157-4_4","article-title":"LC3 and Autophagy","volume":"Volume 445","author":"Tanida","year":"2008","journal-title":"Autophagosome and Phagosome"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.dib.2016.02.085","article-title":"mRNA and Protein Dataset of Autophagy Markers (LC3 and p62) in Several Cell Lines","volume":"7","author":"Pedro","year":"2016","journal-title":"Data Brief"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1083\/jcb.200809125","article-title":"Parkin is Recruited Selectively to Impaired Mitochondria and Promotes Their Autophagy","volume":"183","author":"Narendra","year":"2008","journal-title":"J. Cell Boil."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11805","DOI":"10.1523\/JNEUROSCI.2862-09.2010","article-title":"Parkin Directly Modulates 26S Proteasome Activity","volume":"30","author":"Um","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6788","DOI":"10.1007\/s12035-018-0879-1","article-title":"Parkin in Parkinson\u2019s Disease and Cancer: A Double-Edged Sword","volume":"55","author":"Wahabi","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/j.1471-4159.2011.07318.x","article-title":"Parkin Promotes the Ubiquitination and Degradation of the Mitochondrial Fusion Factor Mitofusin 1","volume":"118","author":"Glauser","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.bbrc.2007.05.093","article-title":"Increased Oxidative Damage and Mitochondrial Abnormalities in the Peripheral Blood of Huntington\u2019s Disease Patients","volume":"359","author":"Chen","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.mito.2014.05.001","article-title":"Reduction in Mitochondrial DNA Copy Number in Peripheral Leukocytes After Onset of Huntington\u2019s Disease","volume":"17","author":"Petersen","year":"2014","journal-title":"Mitochondrion"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Suski, J., Lebiedzinska, M., Bonora, M., Pinton, P., Duszynski, J., and Wieckowski, M.R. (2018). Relation Between Mitochondrial Membrane Potential and ROS Formation. Mitochondrial Bioenergetics, Humana Press.","DOI":"10.1007\/978-1-4939-7831-1_22"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0014-5793(97)01159-9","article-title":"High Protonic Potential Actuates a Mechanism of Production of Reactive Oxygen Species in Mitochondria","volume":"416","author":"Korshunov","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1046\/j.1432-1327.1999.00522.x","article-title":"Effect of Glucose and Deoxyglucose on the Redistribution of Calcium in Ehrlich Ascites Tumour and Zajdela Hepatoma Cells and its Consequences for Mitochondrial Energetics. Further Arguments for the Role of Ca(2+) in the Mechanism of the Crabtree Effect","volume":"263","author":"Wojtczak","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.bbabio.2010.03.005","article-title":"Oxidative Stress-Dependent p66Shc Phosphorylation in Skin Fibroblasts of Children with Mitochondrial Disorders","volume":"1797","author":"Lebiedzinska","year":"2010","journal-title":"Biochim. Biophys. Acta. (BBA) Bioenerg."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1093\/hmg\/ddi319","article-title":"HD CAG Repeat Implicates a Dominant Property of Huntingtin in Mitochondrial Energy Metabolism","volume":"14","author":"Seong","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/hmg\/ddn404","article-title":"Effects of Overexpression of Huntingtin Proteins on Mitochondrial Integrity","volume":"18","author":"Wang","year":"2009","journal-title":"Hum Mol Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/sj.emboj.7601963","article-title":"Fission and Selective Fusion Govern Mitochondrial Segregation and Elimination by Autophagy","volume":"27","author":"Twig","year":"2008","journal-title":"EMBO J."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Seo, H., Sonntag, K.C., Kim, W., Cattaneo, E., and Isacson, O. (2007). Proteasome Activator Enhances Survival of Huntington\u2019s Disease Neuronal Model Cells. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000238"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.neuroscience.2016.02.054","article-title":"Gene Therapy by Proteasome Activator, PA28\u03b3, Improves Motor Coordination and Proteasome Function in Huntington\u2019s Disease YAC128 Mice","volume":"324","author":"Jeon","year":"2016","journal-title":"Neuroscience"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4861","DOI":"10.1093\/hmg\/ddq419","article-title":"Mitofusin 1 and Mitofusin 2 are Ubiquitinated in a PINK1\/Parkin-Dependent Manner Upon Induction of Mitophagy","volume":"19","author":"Gegg","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1083\/jcb.201007013","article-title":"Proteasome and p97 Mediate Mitophagy and Degradation of Mitofusins Induced by Parkin","volume":"191","author":"Tanaka","year":"2010","journal-title":"J. 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